The present invention relates to a protective composition for skin which protects against bacterial, viral and fungal infection In particular, the invention relates to anti-infective (infection preventing) products, to be used to control infections caused by gram positive organisms such as Methicillin Resistant Staphylococcus aureus (MRSA), Pneumococci and Vancomycin Resistant Enterococci (VRE) as well as gram negative bacteria such as Escherichia coli and Pseudomonas aeruginosa. The invention provides a durable handcream which is retained on the hands despite use of the hands. More particularly the invention relates to a protective handcream of the type known as a xe2x80x9cbarrierxe2x80x9d handcream. The invention also provides body lotions, liquid soaps, shampoos, soap bars and creams generally, which are protective.
Although medical science is continually advancing with new techniques and drugs being developed almost daily, cross-infection in hospitals is still a common occurrence with major implications. Micro-organisms may be acquired and transmitted by one of the following routes: direct contact, airborne or via fomites. Although these routes are well understood and procedures to control them are standard practice, pathogenic organisms still exist in the hospital environment.
The spread of infection by direct contact is considered to be the most important method of transmission both for gram positive and gram negative organisms, and it is agreed that the hands of hospital personnel play an important role in the transmission of infection.
Many different organisms exist on the skin. Some belong to the normal flora of the skin and are harmless commensals, which may however, on occasion, become opportunist pathogens in patients who are unusually susceptible to infection such as those in intensive care units. Organisms on the skin can be classified into three categories:
Transient organismsxe2x80x94micro-organisms which are deposited on the skin but do not multiply there,
Temporary residentsxe2x80x94contaminants which multiply on the skin and persist for short periods;
Resident organismsxe2x80x94permanent inhabitants of the skin which colonise the deeper crevices of the skin and hair follicles.
Removal or killing of the transient flora is generally considered sufficient to prevent the transfer of cross-infection in hospital, but removal of the resident flora is an additional advantage which should be achieved if possible.
Skin disturbances lead to difficulties in the process of skin cleansing Patients with eczema are often colonised by Staphylococcus aureus to a greater extent than even those suffering from the strongly scaling disease psoriasis. Patients with an atopic eczema are also more frequently colonised because their skin is not as smooth as those with completely healthy skin. Extensive and frequent use of antiseptic-detergent preparations, such as those used in hospitals, causes moderate to severe drying of the skin of the hands, and indeed small wounds on the fingertips in some cases. Low relative humidity during winter results in additional stress to the skin. More than half the nurses involved in one clinical study had increased numbers of bacteria on their hands after only one week""s use of an antiseptic detergent preparation (Ojajarvi, J. 1978). The increase was thought to be due to the drying and skin damaging effects of frequent hand washing between every patient contact, but the age of the personnel and nature of duties undertaken were also contributory factors.
Currently a source of major concern is the appearance of resistant strains of bacteria which survive the cleansing processes, and which have become resistant to antiseptics, antibacterials and antibiotics which originally destroyed them. No amount of hand washing is capable of removing these micro-organisms. Of particular importance amongst the gram positives are resistant strains of Staphylococcus aureus (Methicillin Resistant Staph. aureusxe2x80x94MRSA), resistant Pneumococci and Enterococci (Vancomycin Resistant Enterococcixe2x80x94VRE).
There is an ever increasing awareness of the need to reduce cross infections in hospitals This awareness has increased with the appearance of these resistant strains The spread of these infections now has enormous consequences for patient care with patients during, hospital stay increasing, and hospital budgets soaring. Drugs used to fight MRSA are now responsible for up to 10% of the drug bill at some U.S. hospitals.
Guidelines prepared by Health Departments around the world recommend, in the absence of anything better, that hand washing is the most important factor currently available in preventing the spread of MRSA and other pathogenic bacteria. These guidelines recommend washing the hands with an antiseptic detergent (e.g. Chlorhexidine-containing hand washes), before and after each patient contact.
The research of Ojajarvi (1978) referred to above shows the limitations of these recommendations. Furthermore, the work of Aly and Maibach (1979) proved that chlorhexidine significantly reduced the normal flora of the hands. These synthetic antiseptic containing preparations suppress the protective gram positive population (Aly and Maibach, 1976), resulting in a potentially harmful shift towards gram negative colonisation. Long-term and frequent use of detergents containing synthetic bacteriostatic agents may lead to detrimental overgrowth of a particular bacterial species which would otherwise have been unable to survive on normal healthy skin.
In addition, allergic contact dermatitis caused by chlorhexidine gluconate and diacetate has been reported by Reynolds et al. (1990) and Knudsen et al.(1991). By far the most alarming problem was the incidence of a hospital outbreak of Chlorhexidine-resistant Proteus mirabilis resulting in an outbreak of urinary-tract infections affecting 90 patients in Southampton between July 1980 and May 1985 (Dance et al. 1987).
These results show that handwashing alone can not prevent the spread of infections.
Boddie et al 1992, J. Dairy Sci. 75 1725-1730 discusses the use of post-milking teat germicides containing Lauricidin (Registered Trade Mark for glycerol monolaurate), saturated fatty acids, lactic acids and lauric acid. Various compositions were determined against new IMI (intra-mammary infection) caused by Staphylococcus aureus and Streptococcus agalactiae in three controlled infection trials.
Each of the compositions contained Lauricidin (TM) and lactic acid. Two of the compositions further contained lauric acid.
Kabara (1983) xe2x80x9cMedium Chain Fatty Acids and Estersxe2x80x9d discusses the history of various types of soaps, and further discusses the suitability of various fatty acids as food additives. It is stated therein that it is well established that unsaturated fatty acids exhibit an antibacterial influence on gram-positive micro-organisms. The inhibitory effects of unsaturated fatty acids are stated to increase as the number of double bonds in the molecule increase.
International Application PCT/US95/02588 (Publication No. WO 95/26710) discusses a personal skin moisturising and cleansing bar composition which comprises both a skin cleansing agent and a lipid moisturising agent in the same bar, which deposits an effective amount of the lipid on the skin of the user in a bath or shower. The bar composition contained both Na lauric soap and lauric acid. The bar thus cleanses and leaves a moisturising lipid layer on the skin. It is not said to have any anti-microbial properties and does not take the form of a leave-on cream or lotion.
U.K. Patent Application No. 675,152 discloses oleaginous cosmetic cleansing creams which are used to loosen and dissolve dirt from the skin and which are easily removed from the skin using water alone. Use in these compositions of monoesters of substantially saturated fatty acids of about 12 to 18 carbon atoms with saturated aliphatic polyhydric alcohols of 2 to 3 carbon atoms is disclosed. The composition of Examples 2 to 7 discloses the use of a para hydroxy benzoic acid as a preservative. It is expressly stated that this preservative proved not to be needed in the formulations of these Examples. The creams are distinct from those of the present invention in that they are designed to be removed from the skin and do not have anti-microbial properties.
German Patent Application No. DE 3 339 196 discloses laurylamido-ethyl-trimethylammonium chloride and its use as an antimicrobial preservative and disinfectant.
U.S. Pat. No 2,900,306 relates to a deodorant stick, comprising a solid alcohol base and having dispersed therein a water soluble soap or salt of saturated higher fatty acids having essentially 12 to 14 carbon atoms. This product is a deodorant not an to anti-microbial cream.
The object of the invention is to produce a product which overcomes all of the above mentioned problems. In particular the object of the present invention therefore is to produce a topical preparation which would be:
supplemental to handwashingxe2x80x94(or in place of where necessary); antibacterialxe2x80x94(against gram positive, especially MRSA and VRE, and gram negative bacteria such as E.coli);
antifungal and antiviral,
of natural origin as far as possiblexe2x80x94(thereby reducing the chance of resistance occurring),
hypoallergenicxe2x80x94(thereby reducing the possibility of contact dermatitis);
acting as a protective xe2x80x9cchemicalxe2x80x9d glovexe2x80x94(thereby always maintaining sterility);
inexpensivexe2x80x94(so as to be affordable to all hospital budgets);
attractive to usexe2x80x94(so that hospital staff will not want to avoid hand sterilization as is currently often the case).
Further objects of the invention are:
(a) To use a naturally occurring compound as active ingredient, which might reduce the incidence of resistance and allergies.
(b) To provide a product that nourishes the skin and thereby prevents drying and skin damage due to frequent use of antibacterial detergents.
(c) To replace natural components of the skin that are vital parts of the antibacterial defence system of the skin that are removed by washing.
(d) To create an active xe2x80x9cliquid glovexe2x80x9d (protective mantle) on the skin that prevents infections by the above mentioned bacterial species.
(e) To provide an attractive, reasonably inexpensive agent that is easy to use and does not require handwashing facilities.
According to the present invention there is provided a protective composition for inhibiting bacterial growth on the skin comprising
(i) a physiologically acceptable carrier or base;
(ii) a preservative,
(iii) an active ingredient for protecting the skin; and
(iv) a skin protectant
characterised in that the active ingredient is selected from a C8 to C20 fatty acid, one or more parabens, or a combination thereof.
The fatty acid is preferably lauric acid or a lauric acid salt such as a sodium salt. The fatty acid is present in an amount of 0.05 to 5% w/v, preferably 0.2 to 1% w/v and more preferably 0.5% w/v.
A paraben or a combination of parabens may be present in the composition. Suitable parabens are methyl and propyl paraben or a combination of methyl and propyl paraben. The composition can suitably contain methyl and propyl parabens in about a 1-1 ratio (w/v). Methyl and propyl paraben are preferably present in an amount of 0.05 to 1% w/v, preferably 0.2 to 0.3% w/v and more preferably 0.25% w/v.
A suitable skin protectant is Simethicone (also known as Dimethicone) Simethicone can be present in an amount of 3 to 10% w/v, preferably 4 to 6% w/v and more preferably 5% w/v.
As an optional extra ingredient, the protective composition may contain an antioxidant, such as Vitamin E (alpha-tocopherol) in an amount of 0.2 to 1% w/v, preferably 0.4 to 0.6% w/v and more preferably 0 5% w/v
The invention also provides the use of a C8 to C20 fatty acid as defined above for use in the manufacture of a protective composition for inhibiting the growth of bacteria, particularly Methicillin Resistant Staphylococcus aureus (MRSA), Vancomycin Resistant Enterococci and gram negative organisms, particularly coliforms and pseudomonants. One or more parabens may also be used to prepare the protective composition.
The invention also provides the use of C8 to C20 fatty acid in the inhibition of bacterial, fungal and viral growth and more particularly the use of such a fatty acid together with one or more parabens to inhibit bacterial, fungal or viral growth.
Suitably the paraben can act both as an active ingredient and as a preservative in the above defined composition. The fatty acids are active against both gram positive and gram negative organisms while parabens are particularly active against gram negative organisms.
In order to achieve the objectives mentioned above it was decided to use products already found in the body and which have been shown to have natural antimicrobial activity. Being naturally occurring they should be hypoallergenic at active concentrations. Certain constituents of milk have been shown to have anti-viral and antibacterial activity (see discussion of Boddie et al, 1992, J. Dairy Sci. 75:1725-1730 above). The active factor appears to be a fatty acid C18:2. Fatty acids and their antimicrobial activity have also been described. Both fatty acids and monoglycerides have these properties and are well documented in the literature. Lactic acid, another naturally occurring component is also known to be inhibitory to both Gram-positive and Gram-negative organisms. A cream in accordance with the invention comprises:
(a) fatty acids (C8-C20) and their salts preferably lauric acid (C12) sodium salt in concentrations of 0.05-5.0%, preferably 0.2 to 1%, more preferably 0.5% w/v.
It is believed that certain derivatives of lauric acid e.g. Lauricidin (glycerol monolaurate) exhibits anti-infective properties in the treatment Intra-Mammary Infections (IMI) as reported by Boddie el al. 1992. Moreover, monoesters of lauric acid are thought to prevent transmission of viruses such as AIDS, hepatitis B and herpes and are therefore used in a liquid antiseptic handwash (GB-B-2193892 of Colgate Palmolive Company) The antiviral activity of milk isolated in the fatty acid fraction has been reported (Kabara, J. J. 1980)
Esters of fatty acids were not incorporated into the product since it is well known that the Fatty Acid Modifying Enzyme (FAME) inactivates a series of bactericidal fatty acids (C11-C24) by esterifying them with certain alcohols as reported by Kapral et al 1992.
(b) A skin protectant. Simethicone (also known as Dimethicone), a mixture of dimethyl polysiloxanes and silica gel, acts as a skin protectant and is used in many established xe2x80x9cskin protectingxe2x80x9d formulations to ensure the retention of the active ingredients on the skin. Here used in a concentration of 3-10%, preferably 4 to 6%, more preferably 5% w/v.
(c) A well-established cream base (oil in water) preserved by a potent antimicrobial preservative system such as Parabens or Nipa Esters(trademark) (available from Nipa Laboratories Ltd., U.K.) (e.g. methyl and propyl paraben sodium salts) with supporting anti-infective properties. The preferred concentration of a 1:1 mixture of parabens is 0.05-1% w/v, preferably 0.2 to 0 3% w/v, more preferably 0.25% w/v.
Parabens are known to be effective in low concentrations against both bacteria and fungi Propylparaben is considered to be antifungal (Merck index)
The cream may also optionally contain.
Vitamin E (alpha-tocopherol) acts as a antioxidant. It is used in concentrations of 0.2-1% preferably 0.4 to 0.6%, more preferably 0.5% w/v. It prevents oxidation of essential cellular constituents and prevents the formation of toxic oxidation products formed from unsaturated fatty acids that have been detected in its absence.
Structures of 
methyl paraben sodium salt (II) and propyl paraben sodium salt (III) 
After washing with an antiseptic detergent or antiseptic soap, if necessary, the barrier cream of the invention is applied by rubbing a fixed, dispensed amount into the hands. The application of further amounts of cream can be done at any stage. The cream has the advantage over normal antiseptic soaps that the active ingredient, once applied, act continuously on the skin and is not washed off, after application, as is the case with the antiseptic soaps. Dispensers for the cream can be placed wherever convenient, and a source of water for washing is not essential. The application of this formulation is not limited to hospitals or consulting rooms but may be used by anyone dealing with the public at large and in danger of infection such as bank tellers, bus conductors, etc. Other possible users are those involved in the production of pharmaceuticals and food products. It is not the intention to replace hand washing altogether but rather to use the cream to maintain sterility after handwashing or in places where hand washing is not possible.
It is also intended that the cream could be used as an antiseptic wound dressing for wounds which are or may become infected by bacteria.
It is also intended that the barrier cream can be applied as a total body application for those patients who are too fragile to move or bath and who might be colonised by bacteria, viruses or fungi, resistant or otherwise.
In a series of tests the moisturising cream base has been found to be highly acceptable to both male and female users indicating that the product will probably be used more often than the use of hand washing with antiseptic soaps.
In a manner similar to that for creams described above, soaps, liquid soaps, body lotions, shampoos or the like, can be made in accordance with the invention.